1. Field of the Invention
The present invention pertains to the field of manipulating microscopic objects such as bacteria, biological cells, neurons, or submicron objects such as virus or nanoparticles, or the like.
2. Discussion of Related Art
The ability to obtain information at the single-cell level is becoming of central importance for numerous biological questions and represents a major challenge. There is an increasing awareness that individual cells, although genetically identical to sister cells, show different phenotypes and expression profiles of genes (transcripts) and in consequence levels of proteins and metabolites. New innovative technologies are required to address individual cells, whereby “to address” has a broad meaning ranging from displacement, injection up to analysis. For the following the focus shall be on the controlled spatial displacement of single cells.
Several years ago A. Ashkin and co-workers pioneered the development of the optical tweezers as mean to manipulate biological objects (see for example EP 307 940). Exploiting the trapping forces due to the radiation pressure through intense and collimated lasers, they showed that one could handle viruses, bacteria, cells up to cellular organellae. Yet, it is still debated at which extent optical tweezers damage the trapped organisms.
Glass micropipettes, the oldest instrument to manipulate single organisms, are not truly apt for displacement experiments. Operated by means of micromanipulators combined with a pressure controller for the suction of the biological objects, their positioning is still followed with optical microscopy which is limited by its intrinsic resolution of the order of 1μ. Consequently, the approach toward an organism without damaging it is a hit-and-miss procedure, while if successfully sucked, it is practically impossible to safely reposition it onto another location of the substrate surface.
The atomic force microscope AFM (G. Binnig, C. F. Quate, and C. Gerber, Phys Rev Lett 56 (9), 930 (1986)) has the required force feedback in the pN range. With respect of organism manipulation, it is employed for a bright spectrum of adhesion experiments but it is not conceived for displacement experiments because organisms are stably attached to the underside of the cantilever preventing their release on another position of the substrate.